Introduction: Sickle cell disease is a public health problem in sub-Saharan Africa. A national referral center for the management of infants and pregnant women with sickle cell disease (CPMI-NFED) was created three de...Introduction: Sickle cell disease is a public health problem in sub-Saharan Africa. A national referral center for the management of infants and pregnant women with sickle cell disease (CPMI-NFED) was created three decades ago in Cotonou, in the south of Benin with two regional branches including that of Parakou in the North for better access of patients to specialized care. This work is a review of five years of activities in order to describe the epidemiological, clinical, hematological and evolutionary profiles of the children followed up in the said branch. Method: This was a descriptive and retrospective cross-sectional study on the medical records of children with sickle cell disease, followed up at the regional branch of CPMI-NFED in Borgou/Alibori from June 1, 2017 to May 31, 2022. The variables studied were epidemiological, clinical, biological and evolutionary. Results: A total of 101 children with sickle cell disease were included in the study, including 78 homozygous SS (77.2%) and 23 heterozygous SC (22.8%). Their mean age at inclusion was 51.2 ± 37.6 months [6 - 204]. The sex ratio was 1.4. Vaso-occlusive crises were the main diagnostic circumstances in 42.3% of homozygotes. More than half of the children (51.5%) had a regular follow-up. The average baseline level of hemoglobin (Hb) in homozygous children was 8.8 ± 1.4 g/dl [5.8 - 11.5];and the rate of Hb S varied between 61.9 and 94.7%. In heterozygous SC children, the mean baseline level of Hb was 10.7 ± 0.6 g/dl [9.7 - 11.5]. Acute complications observed during follow-up were dominated by pneumonia and vaso-occlusive crises in both phenotypes. The overall mortality was 3% and only affected homozygous patients. Conclusion: On average, three out of four children were homozygous in our cohort. The main acute complications were infectious and vaso-occlusive. The mortality only affected homozygous carriers. Specialized follow-up has contributed to improving the quality of life of children with sickle cell disease. This could be implemented on a large scale for better survival of children with sickle cell disease.展开更多
Introduction: Sickle cell disease is a real public health problem in the world and particularly in Niger where the prevalence of the S gene is estimated at 25% and that of the homozygous forms at between 1% and 2%. Tr...Introduction: Sickle cell disease is a real public health problem in the world and particularly in Niger where the prevalence of the S gene is estimated at 25% and that of the homozygous forms at between 1% and 2%. Treatment combines quarterly follow-up of patients and management of complications. The objective of this study was to identify the potential explanatory factors of non-adherence to treatment in sickle cell patients followed at the national reference center for sickle cell disease in Niger. Methods: This is a cross-sectional study of sickle cell cases followed at the CNRD in Niger. The population consisted of all sickle cell patients followed in this center in 2021. The data collection techniques were individual interviews and documentary reviews. Non-adherence was assessed with the Girerd test. Descriptive statistical tests and simple and multiple logistic regression models were performed. Results: A total of 368 patients were enrolled. The median age is 7 years (4;10) and the sex ratio is 1.04. Ninety-eight (98) or 26.6% were compliant and 270 (73.4%) were non-compliant. In multivariate analysis, the factors independently and negatively associated with non-adherence to treatment were schooling (adjusted OR [95% CI], p-value), 0.17 [0.10 - 0.30];p Conclusion: The factors influencing treatment compliance identified in this study are all modifiable. To prevent the complications of sickle cell disease, we must fight against ignorance, make care services accessible and make care free.展开更多
AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospec...AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and December2013.Further requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or radiochemotherapy.The clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of death.Survival times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were calculated.Toxicity and safety were examined.Prognostic factors including ECOG PS,age and previousperioperative treatment were analyzed.RESULTS:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to toxicities.Survival times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,respectively.Survival differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not show a worse outcome in terms of survival.Patients receiving secondline treatment(51%)had a significantly longer RS than patients with best supportive care(6.8 vs 1.4 mo,P=0.001).Initial ECOG PS was a strong prognostic factor for PFS,OS and RS.CONCLUSION:Old patients with non-curable gastroesophageal cancer should be offered chemotherapy,and ECOG PS is a tool for balancing benefit and harm upfront.Second-line treatment is reasonable.展开更多
Recent estimates indicate that one-fifth of botanical species worldwide are considered at risk of becoming extinct in the wild. One available strategy for conserving many rare plant species is reintroduction, which ho...Recent estimates indicate that one-fifth of botanical species worldwide are considered at risk of becoming extinct in the wild. One available strategy for conserving many rare plant species is reintroduction, which holds much promise especially when carefully planned by following guidelines and when monitored long-term. We review the Center for Plant Conservation Best Reintroduction Practice Guidelines and highlight important components for planning plant reintroductions. Before attempting reintroductions practitioners should justify them, should consider alternative conservation strategies, understand threats, and ensure that these threats are absent from any recipient site. Planning a reintroduction requires considering legal and logistic parameters as well as target species and recipient site attributes.Carefully selecting the genetic composition of founders, founder population size, and recipient site will influence establishment and population growth. Whenever possible practitioners should conduct reintroductions as experiments and publish results. To document whether populations are sustainable will require long-term monitoring for decades, therefore planning an appropriate monitoring technique for the taxon must consider current and future needs. Botanical gardens can play a leading role in developing the science and practice of plant reintroduction.展开更多
This study introduces a new global climate model--the Integrated Climate Model (ICM)--developed for the seasonal prediction of East Asian-western North Pacific (EA-WNP) climate by the Center for Monsoon System Res...This study introduces a new global climate model--the Integrated Climate Model (ICM)--developed for the seasonal prediction of East Asian-western North Pacific (EA-WNP) climate by the Center for Monsoon System Research at the Institute of Atmospheric Physics (CMSR, IAP), Chinese Academy of Sciences. ICM integrates ECHAM5 and NEMO2.3 as its atmospheric and oceanic components, respectively, using OASIS3 as the coupler. The simulation skill of ICM is evaluated here, including the simulated climatology, interannual variation, and the influence of E1 Nifio as one of the most important factors on EA-WNP climate. ICM successfully reproduces the distribution of sea surface temperature (SST) and precipitation without climate shift, the seasonal cycle of equatorial Pacific SST, and the precipitation and circulation of East Asian summer monsoon. The most prominent biases of ICM are the excessive cold tongue and unrealistic westward phase propagation of equatorial Pacific SST. The main interannual variation of the tropical Pacific SST and EA-WNP climate E1 Nifio and the East Asia-Pacific Pattern--are also well simulated in ICM, with realistic spatial pattern and period. The simulated E1 Nifio has significant impact on EA-WNP climate, as in other models. The assessment shows ICM should be a reliable model for the seasonal prediction of EA-WNP climate.展开更多
Germinal centers (GC) of secondary lymphoid tissues are critical to mounting a high-affinity humoral immune response. B cells within the GC undergo rapid clonal expansion and selection while diversifying their antib...Germinal centers (GC) of secondary lymphoid tissues are critical to mounting a high-affinity humoral immune response. B cells within the GC undergo rapid clonal expansion and selection while diversifying their antibody genes. Although it is generally believed that GC B cells employ a unique proliferative program to accommodate these processes, little is known about how the GC-associated cell cycle is orchestrated. The D-type cyclins constitute an important component of the cell cycle engine that enables the cells to respond to physiological changes. Cell type- and developmental stage-specific roles of D-type cyclins have been described but the cyclin D requirement during GC reaction has not been addressed. In this study, we report that cyclin D3 is largely dispensable for proliferation and Ig class switching of in vitro activated B cells. In contrast, GC development in Ccnd3^-/- mice is markedly impaired, as is the T cell-dependent antibody response. Within the GC, although both switched and unswitched B cells are affected by cyclin D3 inactivation, the IgM^- pool is more severely reduced. Interestingly, despite a compensatory increase in cyclln D2 expression, a significant number of Ccnd3^-/- GC B cells accumulate in quiescent GO state. Lastly, although cyclin D3 inactivation did not disrupt BCL6 expression in GC B cells, it completely blocked the GC promoting effect of BCL6 overexpression, suggesting that cyclin D3 acts downstream of BCL6 to regulate GC formation. This is the first demonstration that cyclin D3 plays an important and unique role at the GC stage of B cell development.展开更多
Traditional Chinese Medicine (TCM)and Acupuncture & Moxibustion (A & M)originated in China,with a history of severalthousand years.They have made great con-tributions to the human health with theunique theoret...Traditional Chinese Medicine (TCM)and Acupuncture & Moxibustion (A & M)originated in China,with a history of severalthousand years.They have made great con-tributions to the human health with theunique theoretical system and excellent clini-al efficacy,and therefore,are drawing greatattention of the international medicalcircles.At present,TCM and A &展开更多
The Center for Agricultural Resource Research (CARR), the Institute of Genetics and Developmental Biology (IGDB), Chi- nese Academy of Sciences, invites applicants for several research group leader positions. CARR is ...The Center for Agricultural Resource Research (CARR), the Institute of Genetics and Developmental Biology (IGDB), Chi- nese Academy of Sciences, invites applicants for several research group leader positions. CARR is one of the research organizations in Chinese Academy of Sciences (CAS). We seek nominations and applications from individuals who have expertise and a record of accomplishment in research areas related to ecology, agro-hydrology, agro-biology, crop genetics and breeding, and agro-informatics. The successful candidates for the research group leader posi- tions will be expected particularly to farmland water transfer and development of water saving technologies, farmland展开更多
Several phosphoinositide 3-kinase(PI3 K) inhibitors are currently approved to treat hematolymphatic malignant diseases worldwide, and many drugs that have the same target are in the clinical research stage. In March 2...Several phosphoinositide 3-kinase(PI3 K) inhibitors are currently approved to treat hematolymphatic malignant diseases worldwide, and many drugs that have the same target are in the clinical research stage. In March 2022,duvelisib became the first PI3 K inhibitor approved in China indicated for the treatment of hematolymphatic malignant diseases. Meanwhile, linperlisib and copanlisib have almost completed the technical review of the clinical specialty. The Center for Drug Evaluation(CDE) of the China National Medical Products Administration(NMPA) found that class I PI3 K inhibitors can cause various degrees of immune-related adverse events, which are associated with action mechanisms, affecting the benefit-risk assessment of the drugs. On April 21, 2021, the United States Food and Drug Administration(FDA) convened the Oncologic Drugs Advisory Committee(ODAC)meeting to discuss the safety of PI3 K inhibitors indicated for hematolymphatic malignancies and their related risk of death. The hematological tumor group of CDE of the China NMPA summarized and combined the data on PI3 K inhibitors listed or under technical review for marketing authorization applications and found that such products may have unique efficacy and safety characteristics in Chinese patients with malignant lymphoma.展开更多
The China–Sri Lanka Joint Center for Education and Research for the 21 st Century Maritime Silk Road(CSL-CER) was established in August 2015. The Joint Center is an overseas science and education platform establish...The China–Sri Lanka Joint Center for Education and Research for the 21 st Century Maritime Silk Road(CSL-CER) was established in August 2015. The Joint Center is an overseas science and education platform established by Chinese Academy of Sciences. CSL-CER has conducted a series of research activities, including an annual scientific expedition to the eastern Indian Ocean, with many kinds of instruments installed for monsoon and ocean observation. The ‘Numerical Forecast System for the Surrounding Area of Sri Lanka,' which was developed by the Joint Center, can provide rapid mapping on multiple scales and at multiple resolutions for numerical forecast products serving local society. The annual China–Sri Lanka Joint Workshop on Monsoon Climate and Ocean Environment was successfully held in 2015 and 2016. According to the Memorandum of Understanding(MOU) on joint Master's degrees, 15 new Master's students were accepted by University of Chinese Academy of Sciences(UCAS) in 2015.展开更多
The Center for Agricultural Resources Research(CARR),the Institute of Genetics and Developmental Biology(IGDB),Chinese Academy of Sciences,invites applicants for several research group leader positions.CARR is one of ...The Center for Agricultural Resources Research(CARR),the Institute of Genetics and Developmental Biology(IGDB),Chinese Academy of Sciences,invites applicants for several research group leader positions.CARR is one of the research organizations in Chinese Academy of Sciences(CAS).We seek nominations and applications from individuals who have expertise and a record of accomplishment in research areas related to ecology,agro-hydrology,展开更多
Background: Esophageal perforation is a rare, but potentially life threatening injury. The etiology and management of this condition have changed overtime. Iatrogenic causes are increasingly recognized and management ...Background: Esophageal perforation is a rare, but potentially life threatening injury. The etiology and management of this condition have changed overtime. Iatrogenic causes are increasingly recognized and management is evolving towards more conservative approaches. Objective: To review our experience in the management of esophageal perforation in pediatric patients. Patients and methods: This retrospective study was conducted in the Kurdistan center for gastroenterology and hepatology in Sulaimani city. Review of records for cases of esophageal perforation during the period from January 2006 to October 2013 was performed. Results: Ten cases were found to have esophageal perforation. The causes of esophageal perforation were complications of endoscopic dilation for esophageal stricture (n = 7), button battery ingestion (n = 2), complication of esophagoscopy for corrosive injury (n = 1). The mean age was 42 months (range, 18 - 75 months). The diagnosis was made during the procedure in 6 cases, within 12 hours in 2 cases and late in the two cases of battery ingestion. Subcutaneous emphysema and respiratory distress were the main presenting features. The location of perforation was thoracic in 9 cases and cervical in 1 case. Conservative management was successful in 7 patients and surgical closure was done in two patients. One death has been reported. Conclusion: Iatrogenic causes were the most common causes of esophageal perforation. Conservative management with interventions guided by clinical response can have a favorable outcome and may become the best initial treatment strategy in the future. Further larger scale studies are recommended to establish the best protocol for conservative management.展开更多
To:Chinese Association for International Understanding (CAFIU)CONGRATULATIONS LETTER Dear friends,I was glad to receive the news that your institution,our long-term partner,is celebrating its 40th anniversary since th...To:Chinese Association for International Understanding (CAFIU)CONGRATULATIONS LETTER Dear friends,I was glad to receive the news that your institution,our long-term partner,is celebrating its 40th anniversary since the founding of the Association.In the past few years,our two institutions as part of the non-govemmental sector.have jointly done several projects aimed at getting to know each other and especially on the promotion and construction of President Xi Jinping’s big Initiative,"One Belt and One Road".展开更多
World Data Center(WDC)for Seismology,Beijing has developed for 20 years in China until this year.The sustained and stable data sharing service system has already taken shape.This article gives an overview of the const...World Data Center(WDC)for Seismology,Beijing has developed for 20 years in China until this year.The sustained and stable data sharing service system has already taken shape.This article gives an overview of the construction and development of WDC for Seismology,Beijing.It outlines the history,facilities and technical specifications of the center.It also illustrates the data service,the website,and gives a brief description of the perspective.展开更多
Background: Cardiac myxomas are the most frequently encountered benign cardiac tumors that if left untreated are inexorably progressive and potentially fatal. Surgery is the only way of treatment, and if not treated w...Background: Cardiac myxomas are the most frequently encountered benign cardiac tumors that if left untreated are inexorably progressive and potentially fatal. Surgery is the only way of treatment, and if not treated with the right surgical technique recurrence occurs. Objectives: In this single center study we documented the patterns of presentation, localization, surgical approaches and outcome of cardiac myxomas. Methods: This is a retrospective study of 20 patients who underwent surgical removal of atrial myxoma from January 2010 to December 2015. All patients underwent general investigations, and echocardiography was performed on all patients and surgery was done using extracorporeal circulation and mild hypothermia. Results: The ages of the patients ranged from 14 years to 71 years, with a mean of 51.45 years. Most myxomas (75%) originated from left atrium, 20% from right atrium and biatrial in 5% of cases. The male-to-female ratio was 1:2.3 (14 females and 6 males). Myxomas were more common in blood group A+ and B+. Chief complaints were dyspnea (70%) and palpitation (50%). The majority of masses were attached to the interatrial septum (65%) and four of cases (20%) arose from the lateral wall. Right atrial trans-septal incision was used in 55% of cases. No recurrence was recorded in our study. Six patients had postoperative complications, mainly in the form of arrhythmia (3 cases), bleeding (0ne case) and renal failure (one case) which resulted in the death of the patient. Conclusions: Cardiac myxoma excision account for a very small percentage of cardiac procedures. Immediate surgical treatment is indicated because of high risk of embolization and sudden death. Cardiac myxomas can be excised with a low rate of mortality and morbidity. Follow-up examination, including echocardiography, should be performed regularly.展开更多
BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve.The size of the spleen inc...BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve.The size of the spleen increases due to tissue proliferation,fibrosis,and portal vein congestion,which can indirectly reflect the situation of liver fibrosis/cirrhosis.It was reported that the size of the spleen was related to posthepatectomy liver failure(PHLF).So far,there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF.This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area(SPA)for the prediction of PHLF in hepatocellular carcinoma(HCC)patients and to develop a risk prediction model.AIM To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model.METHODS This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022.Within 1 wk before partial hepatectomy,ultrasound examination was performed to measure LS and SPA,and blood was drawn to evaluate the patient’s liver function and other conditions.Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram.Nomogram performance was validated further.The diagnostic performance of the nomogram was evaluated with receiver operating charac-teristic curve compared with the conventional models,including the model for end-stage liver disease(MELD)score and the albumin-bilirubin(ALBI)score.RESULTS A total of 562 HCC patients undergoing hepatectomy(500 in the training cohort and 62 in the validation cohort)were enrolled in this study.The independent predictors of PHLF were LS,SPA,range of resection,blood loss,international normalized ratio,and total bilirubin.Better diagnostic performance of the nomogram was obtained in the training[area under receiver operating characteristic curve(AUC):0.833;95%confidence interval(95%CI):0.792-0.873;sensitivity:83.1%;specificity:73.5%]and validation(AUC:0.802;95%CI:0.684-0.920;sensitivity:95.5%;specificity:52.5%)cohorts compared with the MELD score and the ALBI score.CONCLUSION This PHLF nomogram,mainly based on LS by 2D-SWE and SPA,was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.展开更多
The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided foc...The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.展开更多
AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This mul...AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This multicenter,prospective,randomized,double-masked,parallel-controlled,non-inferiority trial was conducted in three ophthalmology clinical centers in China.Patients with retinal detachment,who were eligible for PPV were consecutively enrolled.Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio.Best-corrected visual acuity(BCVA),intraocular pressure(IOP)measurement,and dilated fundus examination were performed preoperatively and at 1,7±1,28±3d postoperatively.The primary outcome was complete retinal reattachment rate at postoperative day one.The non-inferiority margin was set at 9.8%.The secondary outcomes included intraoperative retinal reattachment rate,and mean changes in IOP and BCVA from baseline to 1,7±1,28±3d postoperatively,respectively.Safety analyses were presented for all randomly assigned participates in this study.RESULTS:Totally 124 eligible patients completed the study between Mar.14,2016 and Jun.7,2017.Sixty of them were randomly assigned to the PFO for ophthalmic surgery group,and 64 were assigned to the F-Octane group.Baseline characteristics were comparable between the two groups.Both groups achieved 100%retinal reattachment at postoperative day one(difference 0,95%CI:-6.21%to 5.75%,P=1).The pre-defined noninferiority criterion was met.No significant difference was observed in intraoperative retinal reattachment rate(difference 1.77%,P=0.61),mean changes in IOP(difference 0.36,-0.09,2.22 mm Hg at 1,7±1,28±3d postoperatively,with all P>0.05)and BCVA(difference 0.04,-0.02,0.06 logMAR at 1,7±1,28±3d postoperatively,all P>0.05)between the two groups.No apparent adverse events related to the utilization of PFO were reported.CONCLUSION:In patients with retinal detachment undergoing PPV,PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade,and both are safe and well-tolerated.展开更多
Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main o...Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main obstacles are associated with the quality of samples used for genomic analysis。展开更多
Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explo...Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.展开更多
文摘Introduction: Sickle cell disease is a public health problem in sub-Saharan Africa. A national referral center for the management of infants and pregnant women with sickle cell disease (CPMI-NFED) was created three decades ago in Cotonou, in the south of Benin with two regional branches including that of Parakou in the North for better access of patients to specialized care. This work is a review of five years of activities in order to describe the epidemiological, clinical, hematological and evolutionary profiles of the children followed up in the said branch. Method: This was a descriptive and retrospective cross-sectional study on the medical records of children with sickle cell disease, followed up at the regional branch of CPMI-NFED in Borgou/Alibori from June 1, 2017 to May 31, 2022. The variables studied were epidemiological, clinical, biological and evolutionary. Results: A total of 101 children with sickle cell disease were included in the study, including 78 homozygous SS (77.2%) and 23 heterozygous SC (22.8%). Their mean age at inclusion was 51.2 ± 37.6 months [6 - 204]. The sex ratio was 1.4. Vaso-occlusive crises were the main diagnostic circumstances in 42.3% of homozygotes. More than half of the children (51.5%) had a regular follow-up. The average baseline level of hemoglobin (Hb) in homozygous children was 8.8 ± 1.4 g/dl [5.8 - 11.5];and the rate of Hb S varied between 61.9 and 94.7%. In heterozygous SC children, the mean baseline level of Hb was 10.7 ± 0.6 g/dl [9.7 - 11.5]. Acute complications observed during follow-up were dominated by pneumonia and vaso-occlusive crises in both phenotypes. The overall mortality was 3% and only affected homozygous patients. Conclusion: On average, three out of four children were homozygous in our cohort. The main acute complications were infectious and vaso-occlusive. The mortality only affected homozygous carriers. Specialized follow-up has contributed to improving the quality of life of children with sickle cell disease. This could be implemented on a large scale for better survival of children with sickle cell disease.
文摘Introduction: Sickle cell disease is a real public health problem in the world and particularly in Niger where the prevalence of the S gene is estimated at 25% and that of the homozygous forms at between 1% and 2%. Treatment combines quarterly follow-up of patients and management of complications. The objective of this study was to identify the potential explanatory factors of non-adherence to treatment in sickle cell patients followed at the national reference center for sickle cell disease in Niger. Methods: This is a cross-sectional study of sickle cell cases followed at the CNRD in Niger. The population consisted of all sickle cell patients followed in this center in 2021. The data collection techniques were individual interviews and documentary reviews. Non-adherence was assessed with the Girerd test. Descriptive statistical tests and simple and multiple logistic regression models were performed. Results: A total of 368 patients were enrolled. The median age is 7 years (4;10) and the sex ratio is 1.04. Ninety-eight (98) or 26.6% were compliant and 270 (73.4%) were non-compliant. In multivariate analysis, the factors independently and negatively associated with non-adherence to treatment were schooling (adjusted OR [95% CI], p-value), 0.17 [0.10 - 0.30];p Conclusion: The factors influencing treatment compliance identified in this study are all modifiable. To prevent the complications of sickle cell disease, we must fight against ignorance, make care services accessible and make care free.
基金Supported by Zentrum für Geriatrische Onkologie und Biologie in der Metropolregion Rhein Neckar(ZOBEL)
文摘AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and December2013.Further requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or radiochemotherapy.The clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of death.Survival times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were calculated.Toxicity and safety were examined.Prognostic factors including ECOG PS,age and previousperioperative treatment were analyzed.RESULTS:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to toxicities.Survival times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,respectively.Survival differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not show a worse outcome in terms of survival.Patients receiving secondline treatment(51%)had a significantly longer RS than patients with best supportive care(6.8 vs 1.4 mo,P=0.001).Initial ECOG PS was a strong prognostic factor for PFS,OS and RS.CONCLUSION:Old patients with non-curable gastroesophageal cancer should be offered chemotherapy,and ECOG PS is a tool for balancing benefit and harm upfront.Second-line treatment is reasonable.
基金Guangxi Chairman's Foundation grant #09203-04 to Hong Liu and colleagues supported JM attendance at the IABG conference possiblefunding from the U.S. Fish and Wildlife Service(1448-40181-99-G173)+4 种基金Florida Department of Agriculture and Consumer Services (#20161,021010,022647)Miami-Dade County Natural Areas Management and Environmentally Endangered Lands Program (R-80807)Arizona Department of TransportationU.S. Forest ServiceU.S. National Park Service
文摘Recent estimates indicate that one-fifth of botanical species worldwide are considered at risk of becoming extinct in the wild. One available strategy for conserving many rare plant species is reintroduction, which holds much promise especially when carefully planned by following guidelines and when monitored long-term. We review the Center for Plant Conservation Best Reintroduction Practice Guidelines and highlight important components for planning plant reintroductions. Before attempting reintroductions practitioners should justify them, should consider alternative conservation strategies, understand threats, and ensure that these threats are absent from any recipient site. Planning a reintroduction requires considering legal and logistic parameters as well as target species and recipient site attributes.Carefully selecting the genetic composition of founders, founder population size, and recipient site will influence establishment and population growth. Whenever possible practitioners should conduct reintroductions as experiments and publish results. To document whether populations are sustainable will require long-term monitoring for decades, therefore planning an appropriate monitoring technique for the taxon must consider current and future needs. Botanical gardens can play a leading role in developing the science and practice of plant reintroduction.
基金supported by the National Basic Research Program of China (Grant Nos.2012CB955604 and 2014CB953903)the National Natural Sciences Foundation of China (Grant No.41375112)
文摘This study introduces a new global climate model--the Integrated Climate Model (ICM)--developed for the seasonal prediction of East Asian-western North Pacific (EA-WNP) climate by the Center for Monsoon System Research at the Institute of Atmospheric Physics (CMSR, IAP), Chinese Academy of Sciences. ICM integrates ECHAM5 and NEMO2.3 as its atmospheric and oceanic components, respectively, using OASIS3 as the coupler. The simulation skill of ICM is evaluated here, including the simulated climatology, interannual variation, and the influence of E1 Nifio as one of the most important factors on EA-WNP climate. ICM successfully reproduces the distribution of sea surface temperature (SST) and precipitation without climate shift, the seasonal cycle of equatorial Pacific SST, and the precipitation and circulation of East Asian summer monsoon. The most prominent biases of ICM are the excessive cold tongue and unrealistic westward phase propagation of equatorial Pacific SST. The main interannual variation of the tropical Pacific SST and EA-WNP climate E1 Nifio and the East Asia-Pacific Pattern--are also well simulated in ICM, with realistic spatial pattern and period. The simulated E1 Nifio has significant impact on EA-WNP climate, as in other models. The assessment shows ICM should be a reliable model for the seasonal prediction of EA-WNP climate.
文摘Germinal centers (GC) of secondary lymphoid tissues are critical to mounting a high-affinity humoral immune response. B cells within the GC undergo rapid clonal expansion and selection while diversifying their antibody genes. Although it is generally believed that GC B cells employ a unique proliferative program to accommodate these processes, little is known about how the GC-associated cell cycle is orchestrated. The D-type cyclins constitute an important component of the cell cycle engine that enables the cells to respond to physiological changes. Cell type- and developmental stage-specific roles of D-type cyclins have been described but the cyclin D requirement during GC reaction has not been addressed. In this study, we report that cyclin D3 is largely dispensable for proliferation and Ig class switching of in vitro activated B cells. In contrast, GC development in Ccnd3^-/- mice is markedly impaired, as is the T cell-dependent antibody response. Within the GC, although both switched and unswitched B cells are affected by cyclin D3 inactivation, the IgM^- pool is more severely reduced. Interestingly, despite a compensatory increase in cyclln D2 expression, a significant number of Ccnd3^-/- GC B cells accumulate in quiescent GO state. Lastly, although cyclin D3 inactivation did not disrupt BCL6 expression in GC B cells, it completely blocked the GC promoting effect of BCL6 overexpression, suggesting that cyclin D3 acts downstream of BCL6 to regulate GC formation. This is the first demonstration that cyclin D3 plays an important and unique role at the GC stage of B cell development.
文摘Traditional Chinese Medicine (TCM)and Acupuncture & Moxibustion (A & M)originated in China,with a history of severalthousand years.They have made great con-tributions to the human health with theunique theoretical system and excellent clini-al efficacy,and therefore,are drawing greatattention of the international medicalcircles.At present,TCM and A &
文摘The Center for Agricultural Resource Research (CARR), the Institute of Genetics and Developmental Biology (IGDB), Chi- nese Academy of Sciences, invites applicants for several research group leader positions. CARR is one of the research organizations in Chinese Academy of Sciences (CAS). We seek nominations and applications from individuals who have expertise and a record of accomplishment in research areas related to ecology, agro-hydrology, agro-biology, crop genetics and breeding, and agro-informatics. The successful candidates for the research group leader posi- tions will be expected particularly to farmland water transfer and development of water saving technologies, farmland
文摘Several phosphoinositide 3-kinase(PI3 K) inhibitors are currently approved to treat hematolymphatic malignant diseases worldwide, and many drugs that have the same target are in the clinical research stage. In March 2022,duvelisib became the first PI3 K inhibitor approved in China indicated for the treatment of hematolymphatic malignant diseases. Meanwhile, linperlisib and copanlisib have almost completed the technical review of the clinical specialty. The Center for Drug Evaluation(CDE) of the China National Medical Products Administration(NMPA) found that class I PI3 K inhibitors can cause various degrees of immune-related adverse events, which are associated with action mechanisms, affecting the benefit-risk assessment of the drugs. On April 21, 2021, the United States Food and Drug Administration(FDA) convened the Oncologic Drugs Advisory Committee(ODAC)meeting to discuss the safety of PI3 K inhibitors indicated for hematolymphatic malignancies and their related risk of death. The hematological tumor group of CDE of the China NMPA summarized and combined the data on PI3 K inhibitors listed or under technical review for marketing authorization applications and found that such products may have unique efficacy and safety characteristics in Chinese patients with malignant lymphoma.
基金funded by the Bureau of International Co-operation, CASsupport provided by the Research Center for Eco-Environmental Sciences, CAS+4 种基金the Institute of Acoustics, CASthe University of Chinese Academy of Sciencesthe University of Ruhunathe University of Peradeniyathe University of Moratuwa
文摘The China–Sri Lanka Joint Center for Education and Research for the 21 st Century Maritime Silk Road(CSL-CER) was established in August 2015. The Joint Center is an overseas science and education platform established by Chinese Academy of Sciences. CSL-CER has conducted a series of research activities, including an annual scientific expedition to the eastern Indian Ocean, with many kinds of instruments installed for monsoon and ocean observation. The ‘Numerical Forecast System for the Surrounding Area of Sri Lanka,' which was developed by the Joint Center, can provide rapid mapping on multiple scales and at multiple resolutions for numerical forecast products serving local society. The annual China–Sri Lanka Joint Workshop on Monsoon Climate and Ocean Environment was successfully held in 2015 and 2016. According to the Memorandum of Understanding(MOU) on joint Master's degrees, 15 new Master's students were accepted by University of Chinese Academy of Sciences(UCAS) in 2015.
文摘The Center for Agricultural Resources Research(CARR),the Institute of Genetics and Developmental Biology(IGDB),Chinese Academy of Sciences,invites applicants for several research group leader positions.CARR is one of the research organizations in Chinese Academy of Sciences(CAS).We seek nominations and applications from individuals who have expertise and a record of accomplishment in research areas related to ecology,agro-hydrology,
文摘Background: Esophageal perforation is a rare, but potentially life threatening injury. The etiology and management of this condition have changed overtime. Iatrogenic causes are increasingly recognized and management is evolving towards more conservative approaches. Objective: To review our experience in the management of esophageal perforation in pediatric patients. Patients and methods: This retrospective study was conducted in the Kurdistan center for gastroenterology and hepatology in Sulaimani city. Review of records for cases of esophageal perforation during the period from January 2006 to October 2013 was performed. Results: Ten cases were found to have esophageal perforation. The causes of esophageal perforation were complications of endoscopic dilation for esophageal stricture (n = 7), button battery ingestion (n = 2), complication of esophagoscopy for corrosive injury (n = 1). The mean age was 42 months (range, 18 - 75 months). The diagnosis was made during the procedure in 6 cases, within 12 hours in 2 cases and late in the two cases of battery ingestion. Subcutaneous emphysema and respiratory distress were the main presenting features. The location of perforation was thoracic in 9 cases and cervical in 1 case. Conservative management was successful in 7 patients and surgical closure was done in two patients. One death has been reported. Conclusion: Iatrogenic causes were the most common causes of esophageal perforation. Conservative management with interventions guided by clinical response can have a favorable outcome and may become the best initial treatment strategy in the future. Further larger scale studies are recommended to establish the best protocol for conservative management.
文摘To:Chinese Association for International Understanding (CAFIU)CONGRATULATIONS LETTER Dear friends,I was glad to receive the news that your institution,our long-term partner,is celebrating its 40th anniversary since the founding of the Association.In the past few years,our two institutions as part of the non-govemmental sector.have jointly done several projects aimed at getting to know each other and especially on the promotion and construction of President Xi Jinping’s big Initiative,"One Belt and One Road".
文摘World Data Center(WDC)for Seismology,Beijing has developed for 20 years in China until this year.The sustained and stable data sharing service system has already taken shape.This article gives an overview of the construction and development of WDC for Seismology,Beijing.It outlines the history,facilities and technical specifications of the center.It also illustrates the data service,the website,and gives a brief description of the perspective.
文摘Background: Cardiac myxomas are the most frequently encountered benign cardiac tumors that if left untreated are inexorably progressive and potentially fatal. Surgery is the only way of treatment, and if not treated with the right surgical technique recurrence occurs. Objectives: In this single center study we documented the patterns of presentation, localization, surgical approaches and outcome of cardiac myxomas. Methods: This is a retrospective study of 20 patients who underwent surgical removal of atrial myxoma from January 2010 to December 2015. All patients underwent general investigations, and echocardiography was performed on all patients and surgery was done using extracorporeal circulation and mild hypothermia. Results: The ages of the patients ranged from 14 years to 71 years, with a mean of 51.45 years. Most myxomas (75%) originated from left atrium, 20% from right atrium and biatrial in 5% of cases. The male-to-female ratio was 1:2.3 (14 females and 6 males). Myxomas were more common in blood group A+ and B+. Chief complaints were dyspnea (70%) and palpitation (50%). The majority of masses were attached to the interatrial septum (65%) and four of cases (20%) arose from the lateral wall. Right atrial trans-septal incision was used in 55% of cases. No recurrence was recorded in our study. Six patients had postoperative complications, mainly in the form of arrhythmia (3 cases), bleeding (0ne case) and renal failure (one case) which resulted in the death of the patient. Conclusions: Cardiac myxoma excision account for a very small percentage of cardiac procedures. Immediate surgical treatment is indicated because of high risk of embolization and sudden death. Cardiac myxomas can be excised with a low rate of mortality and morbidity. Follow-up examination, including echocardiography, should be performed regularly.
基金Supported by the National Natural Science Foundations of China,No.81873897 and No.82102050Shanghai Science and Technology Development Foundation,No.22Y11911500Shanghai Municipal Health Commission of Science and Research Fund,No.202140378.
文摘BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve.The size of the spleen increases due to tissue proliferation,fibrosis,and portal vein congestion,which can indirectly reflect the situation of liver fibrosis/cirrhosis.It was reported that the size of the spleen was related to posthepatectomy liver failure(PHLF).So far,there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF.This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area(SPA)for the prediction of PHLF in hepatocellular carcinoma(HCC)patients and to develop a risk prediction model.AIM To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model.METHODS This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022.Within 1 wk before partial hepatectomy,ultrasound examination was performed to measure LS and SPA,and blood was drawn to evaluate the patient’s liver function and other conditions.Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram.Nomogram performance was validated further.The diagnostic performance of the nomogram was evaluated with receiver operating charac-teristic curve compared with the conventional models,including the model for end-stage liver disease(MELD)score and the albumin-bilirubin(ALBI)score.RESULTS A total of 562 HCC patients undergoing hepatectomy(500 in the training cohort and 62 in the validation cohort)were enrolled in this study.The independent predictors of PHLF were LS,SPA,range of resection,blood loss,international normalized ratio,and total bilirubin.Better diagnostic performance of the nomogram was obtained in the training[area under receiver operating characteristic curve(AUC):0.833;95%confidence interval(95%CI):0.792-0.873;sensitivity:83.1%;specificity:73.5%]and validation(AUC:0.802;95%CI:0.684-0.920;sensitivity:95.5%;specificity:52.5%)cohorts compared with the MELD score and the ALBI score.CONCLUSION This PHLF nomogram,mainly based on LS by 2D-SWE and SPA,was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.
基金sponsored by Insightec Co.Ltd.(Israel)China National Clinical Research Center for Geriatrics,No.NCRCG-PLAGH-2019005 (to LP)
文摘The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.
基金Supported by the Program of Shanghai Academic/Technology Research Leader(No.21XD1402700)the Clinical Research Plan of Shenkang Hospital Development Center of Shanghai(No.SHDC2022CRD001).
文摘AIM:To evaluate the efficacy and safety of perfluoro-n-octane(PFO)for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy(PPV)in management of retinal detachment.METHODS:This multicenter,prospective,randomized,double-masked,parallel-controlled,non-inferiority trial was conducted in three ophthalmology clinical centers in China.Patients with retinal detachment,who were eligible for PPV were consecutively enrolled.Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio.Best-corrected visual acuity(BCVA),intraocular pressure(IOP)measurement,and dilated fundus examination were performed preoperatively and at 1,7±1,28±3d postoperatively.The primary outcome was complete retinal reattachment rate at postoperative day one.The non-inferiority margin was set at 9.8%.The secondary outcomes included intraoperative retinal reattachment rate,and mean changes in IOP and BCVA from baseline to 1,7±1,28±3d postoperatively,respectively.Safety analyses were presented for all randomly assigned participates in this study.RESULTS:Totally 124 eligible patients completed the study between Mar.14,2016 and Jun.7,2017.Sixty of them were randomly assigned to the PFO for ophthalmic surgery group,and 64 were assigned to the F-Octane group.Baseline characteristics were comparable between the two groups.Both groups achieved 100%retinal reattachment at postoperative day one(difference 0,95%CI:-6.21%to 5.75%,P=1).The pre-defined noninferiority criterion was met.No significant difference was observed in intraoperative retinal reattachment rate(difference 1.77%,P=0.61),mean changes in IOP(difference 0.36,-0.09,2.22 mm Hg at 1,7±1,28±3d postoperatively,with all P>0.05)and BCVA(difference 0.04,-0.02,0.06 logMAR at 1,7±1,28±3d postoperatively,all P>0.05)between the two groups.No apparent adverse events related to the utilization of PFO were reported.CONCLUSION:In patients with retinal detachment undergoing PPV,PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade,and both are safe and well-tolerated.
基金the Japan Agency for Medical Research and Development(Grant Nos.20lk0201002j0001,21lk0201005j0001,and 22lk0201007j0001)。
文摘Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main obstacles are associated with the quality of samples used for genomic analysis。
文摘Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.